Nature provides many examples of exquisite protein engineering serving a wide range of functions. There are obvious advantages to copying these designs, however, the resultant peptide-based drugs and materials can be marred by poor in vivo stability and availability, challenging synthesis and high manufacturing costs. The use of chemistry, on the other hand, provides exciting opportunities not only to overcome these problems but also to engineer enhanced chemical, physical and pharmaceutical properties into the native, biologically active or functioning peptide. Towards this end, there is now a growing demand within material science for well-defined protein-polymer hybrids and technology, which can control the primary→tertiary structure of the biomimetic materials. Typically, existing polymerisation processes have failed to address these requirements due to lack of control over structure, polydispersity and/or limited functional group diversity.
Procedures used to generate polymeric peptides include native chemical ligation, radical-induced polymerisation, oxidative polycondensation, and more recently, ruthenium-catalysed metathesis polymerisation (ring opening metathesis polymerisation (ROMP) and acyclic diene metathesis polymerisation (ADMET)). Norbornenyl polymers with pendant cell adhesive peptide sequences were recently synthesised via a ROMP process and ADMET has also been employed to prepare amino acid and peptide-based polymers, termed bio-olefins, for potential applications as biodegradable polymers. Both the ROMP and ADMET strategies produce comb-like polymers comprised of symmetrical olefinic backbones bearing pendant peptide chains. Linear non-peptidic AB-alternating copolymers have also recently been produced via ring opening insertion metathesis polymerisation (ROWIP) and alternating metathesis condensation polymerisation (ALTMET) using acyclic dienes and diacrylates. Structural hierarchy is an important concept in the design of biomaterials, particularly for structural peptide mimics where different foldamers may have specific substrate-binding properties and different biological activities. Recent advances in homogeneous catalysis now provide highly efficient, biocompatible catalysts capable of forming new C—H (hydrogenation) and C—C bonds (metathesis) within peptides, with excellent stereo-, chemo- and regioselectivity. This facilitates the incorporation of specially designed residues and the generation of synthetic materials with new structures, properties and applications.